The goal of the proposed studies is to provide better understanding of the processes of corneal wound-healing at the biochemical and cellular levels. Hopefully with greater understanding, better treatments can then be designed to prevent blindness. Both embryonic development and wound-healing are similarly characterized by cell migration, tissue reabsorption and synthesis of new tissue components. In higher vertebrates, however, the process of wound-healing often fails to regenerate normal tissue. There are at least three possibilities which may account for the failure of healing tissues to recover their normal function: (1) uni-directional cell differentiation; (2) influence of different extracellular matrix in developing and wounded tissues; and (3) influence of different humoral factors in develping and wounded tissues. To examine the possible causes of this failure, the first series of experiments are designed to determine the rates of collagen synthesis and degradation during the healing of lacerated corneas by labeling tissues with [C14]proline and chasing the label with [C12]proline. Furthermore, radioautography will be used to evaluate the role of cells in tissue reabsorption during corneal wound-healing. This will allow us to determine the change of the cell function during corneal wound-healing. In another series of experiments, the injured corneas will be labeled with [H-3]glucosamine and 35SO4 so that the rate of synthesis and degradation proteoglycans can be accessed. To identify factors inhibiting epithelial cell proliferation, lacerated corneas will be cultured in the presence or absence of polymorphonuclear neutrophils (PMN) or conditioned media derived from the cultures of such cells. The corneas will then be labeled with [H-3]thymidine to measure the rate of DNA synthesis. Furthermore, the conditioned media of PMN will be subjected to biochemical analysis to characterize the inhibitor of epithelial cell proliferation. In addition, monoclonal antibodies against different collagen types will be used to determine the possible alteration of the collagen distribution in diseased human eyes.